AB0151 THE ROLE OF PLASMA MICROVESICLES IN LVVs: NOT ONLY BIOLOGICAL MARKERS
Authors: C. Iannone, J. Mason, E. Baldissera, A. Manfredi, E. Tombetti
Journal: Annals of the Rheumatic Diseases (2022)

Background Microvesicles (MVs) are membrane enclosed extracellular vesicles released upon cellular activation and stress, which maintains features and maintain features and constituents of their parental cells. Large vessel vasculitides (LVVs) are inflammatory conditions of the wall of large-sized arteries, mainly represented by giant cell arteritis (GCA) and Takayasu arteritis (TA). Arterial stenosis and dilatation directly affect prognosis and, according to latest EULAR guidelines can be investigated by positron emission tomography and magnetic resonance angiography. Endothelial cells are believed to play a role in the pathogenesis of LVVs and circulating microvesicles could be a biomarker of vessel wall injury. Objectives To verify whether arterial wall derived-MVs detectable in the blood of TA patients and expressing bioactive molecules potentially involved in arterial injury, inflammation and remodeling could correlate with clinical and radiological features of those patients. Methods Platelet was obtained from 112 LVV pts (73 TA, 39 GCA). Plasma flow cytometry was performed with anti-CD14, CD16, anti-CD144 (VE-cadherin, an endothelial marker), anti-CD140a/b (PDGF receptor A/B a vascular stromal marker), anti-HMGB1, anti-PTX3, Mitotracker green and MitoSox, which are expression of mitochondrial moieties and ROS. Vascular imaging was carried out by angio-RM and PET. Circulating microvesicles from LVVs patients were correlated with disease characteristics, namely CRP, NIH activity, PGA, ITAS2010, ITAS2011 activity, immunosuppressant intake (IS), intake of glucocorticoids (yes/no) and biologics, and daily dose of glucocorticoids as well as radiological parameters. Pearson’s and Spearman’s correlation tests were used for parametric and non-parametric analysis. The SPSS IBM Software was used for statistics. Results The number of total MVs negatively correlate to CRP levels positively correlate to IS (p 0.052 and 0.013). CD 14 and 16 + MVs do not correlate with disease activity, extent or vascular inflammation at either MR or PET. PTX3+ MVs positively correlate to disease activity (NIH criteria and VAS), steroid intake, and disease extent (number of vessels at imaging). CD144+ MVs negatively correlate to IS and positively to SUV max at FDG PET. CD140a+ MVs significantly correlate to disease activity (PGA, VAS, and ITAS2010). Mitotracker+ Mvs negatively correlate to SNR max and positively to FDG-PET positivity. Conclusion Monocyte-derived MVs, despite being increased in LVV, do not correlate with disease activity, extent and vascular inflammation. Despite this, endothelial and stromal-derived MVs reflect some disease-related domains including clinical activity and imaging activity at PET. Furthermore, bioactive signals on MVs such as the long pentraxin PTX3 and mitochondria are more promising biomarkers. Accordingly, other studies have shown that systemic pentraxin-3 levels reflect vascular enhancement and progression in Takayasu arteritis, being PCR and ESR more a mirror of the burden of systemic inflammation. However, further studies are required to verify the pathogenic role of MVs in LVVs and to assess the impact of potential confounders such as therapy. References [1]van Niel G et al, Nat Rev Mol Cell Biol. 2018 [2]Mason JC. Nat Rev Rheumatol. 2010 [3]Tombetti et al, Arthirtis Research therapy 2014 Disclosure of Interests None declared